The determination of microscale interaction energies (also called potentials herein) during binding or folding of large molecules, such as proteins and nucleic acids, has been limited by the experimental difficulty of directly measuring atomic-scale interactions within such large molecules. Furthermore the number of interactions involved is very large, as each atom type in one molecule can possibly interact with each atom type in itself (for folding) or the other molecule (for binding). The interaction is often distance dependent, further increasing the number of interactions for which interaction energies are to be determined. For example, if it is assumed that a dozen atom types in one molecule can interact with each of twenty atom types in another molecule at each of 15 different distances, then the number of interaction energies to determine is 3,600. In general, the combinatorially large number of measurements required to comprehensively characterize the potential that describes all possible microscale interactions in a molecular system is at least daunting and expensive, if not prohibitive. As a result of this experimental intractability, interaction energies to date have relied on theoretical models.